The present invention relates to modifying the optical properties of tissue on a transient basis, and more particularly, it relates to a method and apparatus for delivery of a chemical agent to a target tissue, in order to increase the optical transmission through this tissue, on a transient basis.
It is believed that the administered chemical agent displaces the aqueous interstitial fluid of the tissue, thereby effectively altering the interstitial refractive index of the tissue. If the index of refraction of the administered chemical is closer to that of the other components of the tissue, the introduction of this chemical will result in a reduction in the heterogeneity of the refractive indices of the tissue, which in turn reduces the level of scattering within the tissue. Since optical attenuation through the tissue is primarily due to absorption and scattering, a substantial change in scattering dramatically affects the optical attenuation characteristics of most biological tissues.
Previous patents and disclosures relating to the field of this invention have focused on the use of a topical chemical agent for index matching at the tissue-air interface (these prior patents and disclosures are fully identified under the heading “References” at the end of the specifications). For instance, McCarthy, et al. (McCarthy, Fairing, & Buchholz, 1989), disclose the use of an immersion medium (such as glycerol, water, or oil) to match the refractive index of the tissue specimen with that of an objective lens used in their confocal microscope. This approach serves to minimize or eliminate specular reflection, which accounts for approximately 3-4% of loss, when light is irradiated on a tissue-air interface. This approach is well known to one skilled in the art, and Lucas, et al., disclose a similar method as early as 1930 (Lucas, 1930).
The present invention is distinct from the prior art in that it changes the scattering properties of biological tissues, underlying the surface permeability barrier of tissue covering the said biological tissue, by changing the refractive index of the interstitial fluid within the stroma and the entire volume of the covered biological tissue. While topical administration of immersion fluids affects the optical transmission through biological tissues by only 3-4%, the present invention can improve light transmission through biological tissues by up to five or six hundred percent.
The only prior art known to the inventor which teaches enhancement of tissue transparency by topical administration of chemicals is an abstract authored by Chan, et al., and the inventor, in the Fourteenth Annual Houston Conference on Biomedical Engineering Research (Chan, Nemati, Rylander, & Welch, 1996). This abstract teaches the efficacy of this approach for enhancing the transparency of porcine scleral tissue, in order to perform transscleral cyclophotocoagulation on glaucomatous eyes. However, this abstract does not teach bypassing of the most superficial tissue layer (e.g., stratum corneum, for skin, and conjunctiva, for sclera), in order to administer the topical clarifying agents. Without bypassing the outer-most tissue layer, the underlying target tissue layers are impermeable, and the chemicals administered topically to the outermost tissue layer will not reach the interstitial space of the tissue, and therefore will have no impact on the optical properties of the tissue. The authors indicate that a “360° peritomy was performed on the conjunctiva”, but peritomy alone, which is an incision on the conjunctiva at the corneoscleral limbus of the eye, is not sufficient to allow sufficient volume of the clarifying agent to reach the target tissue (in this case, the sclera). In order for this approach to be effective, a full surgical separation of the conjunctiva from the sclera is necessary, to allow the topical chemical agent to permeate into the interstitial space of the sclera.
One of the objects of this invention is to provide a method and apparatus for enhancing optical transmission through biological tissues. Other objects of this invention will become apparent from the specifications, drawings, and by reference to the appended claims.